Xavier Mariette, MD, PhD: Antibody Response in Rituximab-Treated Patients After COVID-19 Vaccination

Rheumatology Network interviewed Xavier Mariette, MD, PhD, to discuss his study “Rituximab impairs B-cell response but not T-cell response to COVID-19 vaccine in auto-immune diseases.” Mariette is affiliated with the Rheumatology department at Bicetre Hospital in Paris, France.

Rheumatology Network: What initially interested your team in comparing humoral and T-cell responses in healthy controls and patients with autoimmune diseases treated with rituximab (RTX) or other immunosuppressants who were vaccinated with the mRNA COVID-19 vaccine?

Xavier Mariette, MD, PhD: We anticipated from the beginning that the antibody response would be impaired as previously published with other vaccines. We did not know if the Pfizer vaccine (BNT162b2) could lead to a good T-cell response.There was no immunological reason to anticipate that the T-cell response would be altered by rituximab, so we decided to investigate the T-cell response. Our technique to measure the T-cell response is also of interest since we were able to dissect the functional cytokine response from CD8 or CD4 T-cells which has been performed by very few other studies.

RN: What was the study design methods your team used?

XM: We performed a prospective, single-center observational study comparing antibody and T-cell response to 2 injections of Pfizer vaccine in healthy volunteers and patients with auto-immune diseases. We divided the patients into 2 groups:

1) Those treated with rituximab (RTX) in the previous year

2) Those treated with other immunosuppressants or immunomodulatory agents

RN: What were the results of your study?

XM: We showed that only 29% of rituximab-treated patients build a neutralizing antibody response compared to 80% of patients treated with other immunosuppressants and 92% of healthy controls. No patient treated with rituximab in the previous 6 months responded.

Regarding the T-cell response, we have reassuring results for our patients treated with RTX. The functional cytokine response of CD4 and CD8 T-cells to SARS-CoV-2 peptides were not different in the RTX group compared to other immunosuppressant groups and healthy controls.

Even if they don’t build an antibody response after vaccination, due to their recent rituximab infusion, they build a perfectly functional CD4 and CD8 T-cell response compared to patients treated with RTX that have an antibody response.

RN: Why do you believe RTX induced diminished antibody response to the mRNA COVD-19 vaccine?

XM: This is due to the destruction of the B-cell population by rituximab treatment that targets CD20 on their surface.

RN: Why does the time since last infusion influence the humoral response in RTX-treated patients so drastically? 

XM: If the RTX infusion is closer than 6 months from the first vaccine dose, the B-cell population is in very low number or absent and is thus unable to differentiate into plasma-cells that will secrete antibodies against SARS-CoV-2.

RN: What is the clinical significance of these results?

XM: Even if our RTX patients don’t always build an antibody response, it is still useful to get them vaccinated to build, at minimum, a T-cell response.

RN: Does your team plan on doing any further research on this topic?

XM: Yes, we are currently analyzing how these patients respond to a third dose of vaccine.

RN: Is there anything else you’d like our audience to know?

XM: We still need to assess if these patients without antibody response to mRNA SARS-CoV-2 vaccines due to RTX and a preserved T- cell response are protected or not against COVID-19.